Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging

Abstract

Fluorine-19 magnetic resonance imaging (19F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metalated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate ('FETRIS') nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the 19F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting 19F MRI detection sensitivity is enhanced by 3-to-5 fold over previously used tracers at 11.7 T, and is predicted to increase by at least 8-fold at clinical field strength of 3 T.

A minimal length rigid helical peptide motif allows rational design of modular surfactants

“…These materials are central components in diverse applications in the pharmaceutical, food, cosmetic and biomedical industry2345. The classical amphiphilic organic surfactants are most often used as components for emulsion preparation, but they exhibit various toxic and irritant properties6.…”

Paramagnetic relaxation enhancement for protein-observed 19F NMR as an enabling approach for efficient fragment screening

“…6,7,37 Other metals may also have favourable properties. Fe(III) has shown promise in some experiments, 38 although T 2 effects may be too substantial for PrOF NMR experiments. 39 In addition to efficient screening of large compound libraries, this method can reduce protein concentration needs, or allow for the use of non-cryogenically cooled NMR probes for PrOF NMR screening.…”

Calcium Fluoride Nanocrystals: Tracers for In Vivo 19F Magnetic Resonance Imaging

“…Thelongitudinal (T 1 )and transverse (T 2 )relaxation times of the 19 Fw ithin the CFP NCs were determined to optimize the acquisition parameters for future 19 Table S2). [25] Although until recently nuclear spins with relatively short T 2 values could not be monitored with conventional MRI acquisition schemes,u ltrashort echo time (UTE) and zero echo time (ZTE) pulse sequences enable MRI of nuclear spin pools with an extremely short T 2 value, [24] including metallated PFCs with 19 FMRI. However,byusing low-flip-angle excitation pulses it was possible to significantly shorten the TR used, allowing increased averaging and thus ah igher signal-to-noise-ratio (SNR) for agiven experiment time.T he 19 FMRs ignal of CFP could be maximized at low flip angles (Ernst angle) at af ixed experiment time,w hile av ery low SNR was obtained when a908 8 pulse was used (TR = 5 T 1 = 48.5 s; Figure 4b).…”

“…Therelatively long T 1 time of CFP may be less favorable for MRI applications owing to the long repetition time (TR) needed to fulfil the 5 T 1 condition for maximizing the MR signal. [25] Next, the feasibility of spatially mapping the distribution of our newly developed water-soluble nanofluorides with 19 FMRI was examined. Thea ddition of ap aramagnetic dopant into the NCs should be considered for the purpose of shortening T 1 ,a sp roposed for PFC nanoemulsions.…”